Thermal fluctuations set fundamental limits on ion channel function

TL;DR

Thermal fluctuations impose fundamental limits on ion channel voltage sensing, affecting single-channel accuracy and collective information capacity, with implications for neuronal computation.

Contribution

This work quantifies how shot noise and Johnson-Nyquist noise set fundamental sensing limits in ion channels, linking physical noise sources to neuronal information processing.

Findings

Shot noise dominates at the single-channel level, limiting voltage sensing accuracy to about 10 mV.

Johnson-Nyquist noise overtakes shot noise at higher channel densities, constraining collective sensing.

The identified noise limits align with measured neuronal channel densities, influencing neuronal computation.

Abstract

Voltage-gated ion channels are essential for propagating signals in neurons. Each channel senses the local membrane potential created by nearby ions. Fluctuations in these ions introduce two fundamental noise sources: (i) shot noise, from the discreteness of ionic charge, and (ii) Johnson-Nyquist noise, from long-wavelength thermal fluctuations of the electric field. We show that, for an individual channel, shot noise dominates and sets an intrinsic limit to voltage sensing. On the $10$ $\mu$s timescales relevant to channel gating, this limit corresponds to an accuracy of about $10$ mV -- close to measured channel sensitivities. When signals from many channels are aggregated, Johnson-Nyquist noise eventually overtakes shot noise and bounds the total information that can be sensed from the environment. This transition occurs at an ion channel density of $< 1$ channel/$\mu$m$^2$ for slow signals and around $10^2-10^4$ channels/$\mu$m$^2$ for signals with $10$ $\mu$s timescales, both of which are within the range of experimentally-measured densities for somas and axon initial segments, respectively. These results provide design principles for single-channel architecture and collective sensing and suggest that neuronal computation is ultimately constrained by thermal fluctuations.